Apparatus for testing pipetting needle linearity in an automated analyzer

ABSTRACT

An analyzer has a horizontally disposed baseplate on which primary containers and secondary containers are disposed, a pipetting needle, a transport device, and a control device. The pipetting needle is formed of an electrically conductive material and is connected to a metering device by a tubing, and is for transferring a predetermined volume of liquid each time from a primary container to a secondary container. The transport device is for the controlled transport of the pipetting needle in three directions at right angles to one another, two of the transport directions extending horizontally and the third transport direction extending vertically. The control device is for controlling the metering device and the transport device. For the purpose of testing the linearity of the pipetting needle the analyzer includes a device for guiding the tip of the pipetting needle around the periphery of the top edge of a reference body (the tip of the pipetting needle is guided at a specific distance from the top edge of the reference body, which distance is a measure of the acceptable curvature of the pipetting needle), and an electrical circuit for detecting electrical contact between the tip of the pipetting needle and the reference body.

BACKGROUND OF THE INVENTION

1. Field

The apparatus and method of the present invention relate to the field ofanalyzers having automated pipetting capability, and more particularly,to analyzers capable of testing the linearity of the pipetting needle.

2. Description

Experience has shown that during operation of an automatic pipettingdevice, deformation of the pipetting needle can occur due to mechanicalloads placed upon the needle, for example, by the intended use of thepipetting needle for piercing sample container lids or reagent containerlids for the withdrawal of samples or reagents, or by inaccuratepositioning of the pipetting needle. Although a very slight curvature ofthe pipetting needle is usually acceptable (some tolerance is providedfor positioning the pipetting needle at the various pipettingpositions), if the curvature of the pipetting needle is greater than thepermissible tolerance, such curvature may result in malfunction of notonly the pipetting device, but also the entire analyzer. Suchmalfunction can occur hours after the analyzer has begun operation andmay cause damage (such as loss of samples and reagents) and expense,including repair costs by the user or an external service, and otherexpenses resulting from the breakdown of the analyzer.

When automatic pipetting devices of the above kind are used, it isdesirable to test the linearity of the pipetting needle by a reliablemethod, for example, after adjustment of the pipetting needle transportdevice and before each operation of the analyzer, thereby allowing thepipetting needle to be replaced before operation, if necessary.

The object of the invention, therefore, is to make available an analyzerand a method of the type indicated hereinbefore which allows forreliable testing of the linearity of the pipetting needle.

According to the invention, the first part of the above problem issolved by an analyzer having:

means for guiding the tip of the pipetting needle around the peripheryof the top edge of a reference body, the tip of the pipetting needlebeing guided at a specific distance d from the top edge of the referencebody, which distance is a measure of the acceptable curvature of thepipetting needle, and

an electrical circuit for detecting an electrical contact between thetip of the pipetting needle and the reference body.

According to the invention, the second part of the above problem issolved by a method for testing the linearity of the pipetting needle,which is characterized in that:

the tip of the pipetting needle is guided around the periphery of thetop edge of a reference body, the tip of the pipetting needle beingguided at a specific distance d from the top edge of the reference body,which distance is a measure of the acceptable curvature of the pipettingneedle, and

any contact between the reference body and the pipetting needle isdetected by means of an electrical circuit.

A major advantage of the analyzer and method according to the inventionis that it gives very reliable testing of the linearity of the pipettingneedle.

SUMMARY OF THE INVENTION

The subject invention provides an analyzer having a base plate, ametering device, a pipetting needle, a transport device, a referencebody, and a control device.

The horizontally disposed baseplate has primary containers and secondarycontainers disposed thereon. The metering device is for measuring apredetermined volume of a liquid. The pipetting needle is fortransferring a predetermined volume of liquid from a primary containerto a secondary container. The pipetting needle is formed of anelectrically conductive material and is connected by tubing to themetering device. The transport device is for the controlled transport ofthe pipetting needle in three directions at right angles to one another,two of the transport directions extending horizontally and the thirdtransport direction extending vertically. The electrically conductivereference body has a top edge and is positioned at a predeterminedlocation. The control device is for controlling the metering device andthe transport device.

The control device has means for guiding the tip of the pipetting needlearound the periphery of the top edge of the reference body, and anelectric circuit between the pipetting needle and the reference body.The tip of the pipetting needle is guided at a specific distance fromthe top edge of the reference body. The distance is a measure of theacceptable curvature of the pipetting needle. The electrical circuitbetween the pipetting needle and the reference body, detects anelectrical contact between the tip of the pipetting needle and thereference body.

Also provided is a method of testing the linearity of the pipettingneedle in an automatic pipetting analyzer having an electricallyconductive reference body with a top edge, and a transport deviceadapted to move the pipetting needle in three directions at right anglesto one another. The method comprises two steps. The first step isguiding the tip of the pipetting needle around the periphery of the topedge of the reference body at a specific distance from the top edge ofthe reference body. The distance is a measure of the acceptablecurvature of the pipetting needle. The second step is detecting anycontact between the reference body and the pipetting needle. Contactindicates that the pipette needle has unacceptable linearity.

BRIEF DESCRIPTION OF THE FIGURES

One exemplified embodiment of the invention is described below withreference to the accompanying drawings.

FIG. 1 is a perspective view of an analyzer.

FIG. 2 is a plan view of the analyzer shown in FIG. 1.

FIG. 3 is a perspective diagrammatic view of the arrangement of thesample containers, reagent containers and reaction containers in theanalyzer 11.

FIG. 4 is an enlarged perspective view of one of the reaction containers31 in FIGS. 1-3.

FIG. 5 is an illustration of the reaction container 31 of FIG. 4 showingthe interior thereof.

FIG. 6 is a diagram of the scanning of the reference body 45 by apipetting needle 42.

FIG. 7 is a diagram showing the movement of the pipetting needle 42 in ahorizontal direction (X and Y directions) during the scanning operationshown in FIG. 6.

FIG. 8 is a diagram showing scanning in the vertical direction (Zdirection) of the top surface of a reference body with a pipettingneedle.

FIG. 9 is a diagram showing an arrangement for measuring the capacitancebetween the pipetting needle 42 and the reference body 45.

FIG. 10 is an equivalent circuit diagram of the arrangement shown inFIG. 9.

FIG. 11 is a diagram showing the variation of the electrical capacitancebetween the pipetting needle 42 and the reference body 45.

FIG. 12 is a diagram showing the guidance of a pipetting needle 42according to the invention around a reference body 45 for the purpose oftesting the linearity of the pipetting needle.

FIG. 13 is a diagram showing the position of the pipetting needle 42 inthe vertical direction (Z direction) during the guidance of thepipetting needle 42 around the reference body 45 as shown in FIG. 12.

DETAILED DESCRIPTION OF THE INVENTION

The subject invention will now be described in terms of its preferredembodiments. These embodiments are set forth to aid in understanding theinvention, but are not to be construed as limiting.

The invention relates to an analyzer comprising the followingcomponents:

a horizontally disposed baseplate on which primary containers andsecondary containers are disposed,

a pipetting needle having an electrically conductive material andconnected to a metering device by a tubing, for transferring apredetermined volume of liquid each time from a primary container to asecondary container,

a transport device for the controlled transport of the pipetting needlein three directions at right angles to one another (the X, Y and Zdirections), two of the transport directions (X and Y directions)extending horizontally and the third transport direction (Z direction)extending vertically, and

a control device for controlling the metering device and the transportdevice.

The invention relates more particularly to the construction of thetransport device for the pipetting needle of the pipetting device of anautomatic analyzer, such as an analyzer for analyzing biologicalsamples.

The invention also relates to a method for the automatic transport of apipetting needle 42 of an automatic pipetting device of an analyzer to anumber of pipetting positions by means of a transport device 51-55, eachpipetting position corresponding to the position of a specificcontainer, the transport device 51-55 being adapted to move thepipetting needle 42 in three directions (X, Y, Z) at right angles to oneanother, each of said directions being parallel to one of the coordinateaxes of the coordinate system of the transport device 51-55.

A typical pipetting operation in an automatic analyzer is removal of aspecific reagent volume from a primary container, such as a reagentcontainer, and its delivery to a secondary container, such as a reactioncontainer. Under these conditions, a transport device brings thepipetting needle from one target position to the next. In each targetposition, the automatically controlled metering device effects therequired removal or delivery of a liquid volume.

In the three-dimensional right-angled coordinate system of the transportdevice, the primary and secondary containers are disposed in containerreceptacles on carrier plates which are parallel to the XY-plane of thecoordinate system. When the transport device brings the pipetting needleinto a target position, the device first moves the pipetting needle in aplane parallel to the XY-plane until it is above the target containerand then lowers the pipetting needle until it is in the correct positionfor withdrawal of liquid from a primary container or delivery of liquidto a secondary container.

To enable the transport device to bring the pipetting needle to an exacttarget position in the XY-plane, that is, exactly above a primary orsecondary container, the following conditions should be met:

the transport device control means should receive the X and Ycoordinates of the target position as an input signal in order to beable to control the transport device appropriately,

the primary and secondary containers should be at the exact position,

the transport device should be adjusted in each transport direction,that is, each transport direction there should be a defined positionapplicable as a reference position.

Analyzer

FIG. 1 is a perspective view of an analyzer 11. The device comprises ahorizontal baseplate 12, on which are disposed primary containers, suchas sample containers 13 and reagent containers 23, and secondarycontainers, such as reaction containers 31. The analyzer 11 contains anautomatic pipetting device, in which a pipetting needle 42 consists ofan electrically conductive material connected to a metering device 96 bytubing 99. The metering device is preferably an automatically controlledmetering syringe contained in the transport head 51 explained below.

A predetermined volume of liquid is transferred by the pipetting needle42 from a primary container 13 or 23 to a secondary container 31. Thepipetting device contains a transport device 51-55 for the controlledtransport of the pipetting needle 42 in three directions at right anglesto one another, the X, Y and Z directions. Two of the transportdirection (X and Y), are horizontal, and the third direction (Z) isvertical. The transport device contains a transport head 51 whichcontains a drive 52 for transporting the pipetting needle 42 vertically.The transport head 51 preferably also contains a drive 53 fortransporting a gripper 43 vertically. By means of this gripper, reactioncontainers can be transported to different processing positions, suchas, from a loading position in which the reaction containers are chargedwith samples and reagents, to an incubator 36 contained in the analyzer,and from there to a washing device 62 also contained in the analyzer, orto a photometer 61.

The transport head 51 is movable by a suitable drive in the X directionalong a rail 55. Rail 55 is movable by a suitable drive in the Ydirection along rails 54 (see FIG. 2). Rails 54 are fixed on thebaseplate 12.

The analyzer contains an electrically conductive reference body 45rigidly connected to the baseplate 12 and having two outer surfaces 76,77 and 78, 79, respectively, in each of the horizontal transportdirections, (the X and Y directions), the outer surfaces being disposedperpendicularly to the direction of transport. The reference body 45 isused for the fine adjustment of the pipetting needle transport device51-55 as described below. The reference body 45 is preferably a squarebolt of square cross-section.

A carrier plate 21 is disposed on the baseplate 12 and variouscontainers are disposed thereon. As shown in FIGS. 1 to 3, the followingcontainers, for example, are disposed on carrier plate 21:

sample containers 13 in sample container holders 16, 17, 18 which are inturn disposed in a sample container holder unit 15,

reagent containers 23, 24 in reagent container holders 25, 26, 27, and

reaction containers 31 in reaction container holders 33, 34, 35.

As shown in FIG. 3, the sample containers 13 can, for example, bedisposed in a circular arrangement 14 received in one of the samplecontainer holders. Each of the sample containers 13 has a lid which canbe pierced by the pipetting needle. Each of the sample container holders16, 17, 18 has a lid formed with apertures through which the pipettingneedle has access to the sample container lids. The pipetting operationsare performed with the sample containers closed.

As will be seen from FIG. 3, each of the reagent containers 23, 24 isclosed by an appropriate lid. These lids can also be pierced by thepipetting needle. Thus, pipetting operations are performed with thereagent containers closed.

FIG. 4 is an enlarged perspective view of one of the reaction containers31 of FIGS. 1 to 3. FIG. 5 is an illustration of the reaction container31 of FIG. 4 to show the interior of the reaction container.

Analyzer control Unit

All operations which are to be performed, including control of themetering device 96 and transport device 51-55, are controlled andcoordinated by a central analyzer control unit (not shown). A controlsurface 64 or keyboard for inputting process parameters, and a displayto display process states, are shown diagrammatically. The sample dataapplied to the sample tubes, for example, by bar coding, can be readinto a memory via a manually held reading pen or scanner 63. Interfacesfor a printer etc (not shown) are provided.

Means for adjusting the transport device 51-55

The embodiments of the analyzer 11 described below contain means forrough adjustment of the transport device 51-55 of the pipetting needle42. For this purpose, for example, means are used by which the pipettingneedle 42 is guided into an end position and the coordinates (Xe, Ye,Ze) of the end position of the pipetting needle in each of the threedirections at right angles to one another are detected and stored. Theend position of the pipetting needle 42 in the X and Y directions isdefined by the corresponding end position of the transport head 51. FIG.2 shows the transport head 51 in its end position in the X and Ydirections. The end position of the transport head 51 in the X directionis detected by suitable means when the transport head 51 reaches thestop 56. The end position of the transport head 51 in the Y direction isdetected by suitable means when the transport head 51 reaches the stop57. The highest possible position of the pipetting needle permitted byits drive 52 defines the end position of the pipetting needle in the Zdirection. The fact that the end position of the transport head 51 hasbeen reached in each transport direction is detected by suitable means,such as, by an electric signal triggered by the contact between thetransport head 51 and a stop and fed to the analyzer control unit.

The broken lines in FIG. 2 show the basic position 58 of the transporthead 51 in the X direction and the basic position 59 of the rail 55 inthe Y direction.

The analyzer 11 also contains the following means for fine (veryaccurate) adjustment of the transport device 51-55:

a circuit for measuring the electrical capacitance between the pipettingneedle 42 and the reference body 45, and

means for determining the coordinates of a reference position of thepipetting needle 42 in at least one of the horizontal transportdirections, (X and Y), said means being adapted so to move the transportdevice 51-55 of the pipetting needle 42 so that the latter is moved inopposite directions in each case to a position near each of the twoouter surfaces 76-79 of the reference body 45 which are disposedperpendicularly to the direction of transport, the pipetting needle 42being moved in each case towards one surface of the reference member 45until the value of the electrical capacitance between the pipettingneedle 42 and the reference body 45 as measured by the circuit reaches apredetermined value corresponding to a specific distance between thepipetting needle 42 and the surface of the reference body 45.

As shown in FIG. 6, the scanned zone of the reference body 45 preferablyhas a square cross-section in a plane perpendicular to the longitudinalaxis of the reference body 45.

The electrical resistance of the liquid contained in the tubing 99connecting the pipetting needle 42 to the metering system 96 (see FIG.9) is preferably larger than a predetermined limit.

1st preferred embodiment of the means for fine adjustment of thetransport device 51-55.

A first preferred embodiment of the analyzer also contains the followingmeans:

means for detecting and storing the coordinate values of the two thusdefined positions of the pipetting needle 42 in the at least onehorizontal transport direction, (X and/or Y), and,

means for determining the coordinates of a reference position in thetransport direction by calculating the average of the two coordinatevalues detected.

After the reference position coordinates have been determined, the Xarid Y coordinates of all the pipetting positions of the pipettingneedle with respect to the coordinates of the reference position arecalculated in the above-mentioned control unit by reference to therelevant dimensions of the different parts of the analyzer.

2nd preferred embodiment of the means for fine adjustment of thetransport device 51-55

A second preferred embodiment of the analyzer contains means fordetermining the coordinates Xo, Yo of a reference axis extendingparallel to the vertical transport direction Z and through the referencebody 45, said means being adapted so to move the transport device 51-55of the pipetting needle 42 that the latter is moved in the twohorizontal transport directions (X and Y directions) and in oppositedirections in each case to a position near each of the two outersurfaces 76-79 of the reference body 45 which are disposedperpendicularly to the transport direction, the pipetting needle 42being moved in each case towards a surface of the reference body 45until the value of the electrical capacitance between the pipettingneedle 42 and the reference body 45 as measured by the circuit reaches apredetermined value corresponding to a specific distance between thepipetting needle 42 and the surface of the reference body 45.

After the coordinates Xo, Yo of the above-mentioned reference axis havebeen determined, the X and Y coordinates of all the pipetting positionsof the pipetting needle with respect to Xo, Yo are calculated in theabovementioned control unit by reference to the relevant dimensions ofthe different parts of the analyzer.

This second preferred embodiment preferably additionally contains thefollowing means:

means for detecting and storing the coordinate values of the two thusdefined positions of the pipetting needle 42 in each of the horizontaltransport directions (X and Y directions), and

means for determining the coordinate values of a reference position ineach of the horizontal transport directions (X and Y directions) bycalculating the average of the two detected coordinate values.

Circuit for measuring the capacitance between the pipetting needle andthe reference body (FIGS. 9, 10 and 11)

A circuit, as shown in FIG. 9, is used to measure electrical capacitancebetween the pipetting needle 42 and the reference body 45. This circuitis also used in the analyzer as part of a level detector. A leveldetector is used to control the depth of immersion of the pipettingneedle during pipetting operations (such as, on withdrawal of a samplevolume from a sample container) by measuring the electrical capacitancebetween the pipetting needle and the surface of the liquid sample sothat only a very short segment of the tip of the pipetting needle isimmersed in the liquid sample. Thus, the amount of sample undesirablyentrained at the outer surface of the pipetting needle is as small aspossible. In addition to its own function as part of the pipettingdevice, the pipetting needle under these conditions has the additionalfunction of being part of the electrical measuring circuit by means ofwhich the electrical capacitance between the pipetting needle and thesurface of the liquid sample is measured.

As will also be seen from FIG. 9, the pipetting needle 42 is in liquidconnection with the liquid in a liquid container 91 via a tube 99, aconnector 98 and a T-piece 95 having a metering syringe 96, and by avalve 94, a pump 93 and tubing 92. All these components form a liquidsystem which is filled with the liquid contained in the liquid container91 during operation of the pipetting device. In the present exemplifiedembodiment, this liquid has good electrical conductivity.

Tube 99 is disposed in a guarding case 101. The connector 98 ismechanically and electrically connected to the case 101 and to theliquid in the tubing 97.

As will also be seen from FIG. 9, the pipetting needle 42 iselectrically connected to the input of an oscillator circuit 104 by theinternal conductor of a coaxial cable 103. The oscillator circuit 104contains an impedance transformer 105 and a voltage comparator 106connected thereto. A coupling resistor R1 connects the output of thevoltage comparator 106 to the input of the impedance transformer 105.The electrical connection between the output of the impedancetransformer 105 and the voltage comparator 106 is electrically connectedto the outer conductor of the coaxial cable 103 and via a line 102("guard") to the guarding case 101 and to the liquid in the tubing 97.The guarding case 101 and the guard 102 serve for electrical decouplingof the circuit for measuring the capacitance C2 between the pipettingneedle 42 and the reference body 45 from the above-mentioned pipettingdevice liquid system. In this way, the function of the circuit formeasuring the capacitance C2 between the pipetting needle 42 and thereference body 45 is rendered insensitive to stray capacitances, whichwould otherwise influence the function of the measuring circuit by themechanical and liquid connection of the pipetting needle 42 to theabove-mentioned liquid system.

As shown diagrammatically in FIG. 9, the reference body 45 ismechanically and electrically connected directly to a baseplate 12 ofthe analyzer (see FIG. 1). The baseplate 12 is electrically grounded.

In FIG. 9, C2 represents capacitance between the pipetting needle 42 andthe reference body 45. C3 represents capacitance between the oscillatorcircuit 104 and earth. In FIG. 10, C1 represents capacitance between thepipetting needle 42 and earth, when the pipetting needle is in aspecific vertical position--such as, the position shown in FIG. 7--butso far away from the reference body 45 that C2 is practically zero. Inthe present example C1=4 picofarad.

FIG. 10 shows an equivalent circuit diagram of the arrangement shown in

FIG. 9. In FIG. 10, R2 represents the electrical resistance of theliquid in the tube 99 in FIG. 9.

FIG. 11 shows the variation of the capacitance C2 in picofarad as afunction of the distance between the pipetting needle 42 and thereference body 45.

The oscillatory frequency f of the oscillator 104 is given by thefollowing formula:

    f=1/T=1/2*R1(C1+C2)

The oscillatory frequency f of the oscillator 104 is, for example, 120kilohertz when R1=1 megaohm C1=4 picofarad and C2=0 picofarad.

Of course, f can have other values. Considerably higher values of f, forexample in the megahertz range, are disadvantageous because theinfluence of interference signals becomes excessive. Considerably lowervalues of f are also disadvantageous because more time is required forevaluation of the oscillator circuit output signal.

FIG. 10 shows, among other things, the waveforms at three points of theequivalent circuit diagram of the oscillator circuit 104 according toFIG. 9. The waveform at the input and output of the impedancetransformer 105 is due to the fact that the RC network of the oscillatorcircuit is continuously charged and discharged at a time constant t,where t=2* RI(C1+C2).

When the pipetting needle 42 approaches one of the lateral outsidesurfaces of the reference body 45, the value of C2 according to FIG. 11increases and this results in a corresponding change of the value of f.By measuring the frequency f of the signal at the output of the voltagecomparator 106 it is therefore possible to measure the value of C2 andhence determine the corresponding distance between the pipetting needle42 and the outside side surfaces of the reference body 45. For thispurpose, the value of C2 is first measured for a specific position ofthe pipetting needle 42 in the analyzer 11. This specific position ofthe pipetting needle is, for example, the position 71 shown in FIGS. 6and 7, in which the distance S71 between the pipetting needle 42 and thereference body 45 is 3 millimeters. The corresponding value of C2 isgiven the reference C71 in FIG. 11.

For a suitable function of the impedance transformer 105 it is importantthat the resistance R2 of the liquid in the tube 99 should not dropbelow a present critical value of 100 kiloohm. Otherwise R2 would be toohigh a load on the impedance transformer 105. Too low a value of R2 maybe due to the liquid in the liquid system of the pipetting device havinga very low resistivity. By suitable choice of the parameters determiningthe value of R2, however, it is possible to obtain a value for thisresistance to satisfy the above condition.

The value of R2 is given by R2=r*1* 4/(p d²), where

r=resistivity of the liquid in the tube 99

l=length of tube 99

d=inside diameter of tube 99

If r=0.26 ohm*meter, 1=0.76 meter and d=0.76 mm, R2=263 kiloohm

Mode of operation of analyzer

With an analyzer, the pipetting needle 42 of the automatic pipettingdevice of the analyzer 11 is brought to a number of pipetting positionsby means of a transport device 51-55, each pipetting positioncorresponding to the position of a specific container, the transportdevice 51-55 being adapted to move the pipetting needle 42 in threedirections at fight angles to one another (X, Y and Z), each of thesedirections being parallel to one of the coordinate axes of thecoordinate system of the transport device 51-55.

Before the fine adjustment of the pipetting needle transport device51-55 as described below, rough adjustment thereof is carried out, forwhich purpose the pipetting needle 42 is brought by the transport device51-55 to the above-defined end position in each of the three directionsat right angles to one another and the coordinates (Xe, Ye, Ze) of theend position are detected and stored.

For fine (accurate) adjustment of the pipetting needle transport device51-55, coordinates of reference points are determined. The electricallyconductive reference body 45 is used for this purpose, and is rigidlyconnected to the baseplate 12 and has in each of the horizontaltransport directions (X and Y directions) two outer surfaces 76-79,which are disposed perpendicularly to the transport direction.

For the fine (accurate) adjustment of the pipetting needle transportdevice 51-55, the following steps are carried out:

the electrical capacitance C2 between the pipetting needle 42 and thereference body 45 is measured with the above-described circuit, thevalue of C2 first being measured for a specific position 71 of thepipetting needle 42 in the analyzer 11. This specific position of thepipetting needle is, for example, the position 71 shown in FIGS. 6 and7, in which the distance S71 between the pipetting needle 42 and thereference body 45 is 3 millimeters. The corresponding value of C2 isgiven the reference C71 in FIG. 11. As will be seen from FIG. 11, forexample, C71 is 0.7 picofarad and

to determine the coordinates of a reference position of the pipettingneedle 42 in at least one of the horizontal transport directions (X andY directions), the pipetting needle 42 is moved by the transport device51-55 in opposite directions in each case to a position near each of thetwo outer surfaces 76, 77; 78, 79 of the reference body 45 which aredisposed perpendicularly to the transport direction. In theseconditions, the pipetting needle 42 is moved, for example, in the Ydirection first towards an outer surface 76 of the reference body 45until the pipetting needle reaches a position 72, in which the measuredvalue of the electrical capacitance C2 between the pipetting needle 42and the reference body 45 reaches a predetermined value C72corresponding to a specific distance S72 between the pipetting needle 42and the outer surface 76 of the reference body 45. The coordinate of theposition 72 in the Y direction is Y72. This operation is then carriedout in the opposite direction, that is, the pipetting needle 42 is movedin the Y direction towards a surface 77 of the reference body 45 untilthe pipetting needle reaches a position 73 in which the measured valueof the electrical capacitance C2 between the pipetting needle 42 and thereference body 45 reaches a predetermined value C73 corresponding to aspecific distance S73 between the pipetting needle 42 and the outersurface 77 of the reference body 45. The coordinate of the position 73in the Y direction is Y73. In the context of the invention, C73 ispreferably equal to C72 and S73 is equal to S72. As will be seen fromFIG. 11, for example, C73=C72=1.2 picofarad.

In the above-described method, and in the embodiments described below,the pipetting needle during its entire guided movement is situatedagainst one of the lateral outside surfaces of the reference body 45preferably in the vertical position (the Z direction) shown in FIG. 7,in which a considerable part of the pipetting needle lies opposite theouter surface. In this way, the capacitance C2 has a sufficiently highvalue. Also, as a result of the vertical position of the pipettingneedle as shown in FIG. 7, adjustment accuracy is very high,particularly for the top part of the pipetting needle. This is a resultof the adjustment the top part of the pipetting needle is positionedwith the maximum accuracy at the different pipetting positions. Thepresent exemplified embodiment affords the additional advantage that thegripper 43, carried and guided by the transport head 51, is alsopositioned with maximum accuracy at the different positions where itholds and moves the reaction containers 31.

After the determination of the coordinates of a reference position ofthe pipetting needle in the X and Y directions, including fineadjustment in at least one of the horizontal transport directions (X andY directions), a reference position in the Z direction is defined inwhich the pipetting needle 42 is moved from its initial position in thehighest position and with decreasing speed towards the center of the topsurface 46 of the reference body 45 until the tip of the pipettingneedle touches the surface 46 and this contact is detected by a suitablecircuit. The reference position thus determined for the pipetting needlein the Z direction is stored.

1st preferred embodiment of the method for fine adjustment of thetransport device 51-55

In a first preferred embodiment of the method for fine adjustment of thetransport device 51-55, the coordinate values of the two thus definedpositions of the pipetting needle 42 in the at least one horizontaltransport direction are detected and stored. The coordinate values of areference position in the at least one horizontal transport directionare determined by calculating the average of the two detected coordinatevalues, e.g. Y72 and Y73.

Determination of the positions 71 and 73 on opposite sides of thereference body 45 and the above-mentioned calculation of the average ofthe two detected coordinate values have the advantage that the symmetryof the reference body is thus utilized in order to eliminate theinfluence of any inaccuracies in the capacitance measurement on thecalculated coordinate values of the reference position.

After the coordinates of the reference position have been determined,the X and Y coordinates of all the pipetting positions of the pipettingneedle with respect to the coordinates of the reference position arecalculated in the above-mentioned control unit by reference to therelevant dimensions of the different parts of the analyzer.

2nd preferred embodiment of the method for fine adjustment of thetransport device 51-55

In a second preferred embodiment of the method for fine adjustment ofthe transport device 51-55, the coordinates Xo, Yo of a reference axisare determined, such axis extending parallel to the vertical transportdirection (Z) and through the reference body 45. For this purpose, thepipetting needle 42 is moved by the transport device 51-55 in twohorizontal transport directions (X and Y directions) in each case to aposition near each of the two outer surfaces 76-79 of the reference body45 which are disposed perpendicularly to the transport direction, thepipetting needle 42 being moved in each case towards one surface of thereference body 45 until the measured value of the electric capacitancebetween the pipetting needle 42 and the reference body 45 reaches apredetermined value corresponding to a specific distance between thepipetting needle 42 and the surface of the reference body 45.

Within the context of this method, for example, in addition to theabove-described detection of specific reference points of the pipettingneedle in the Y direction, the same method is performed in the Xdirection.

For this purpose, the pipetting needle is first moved towards a surface74 of the reference body 45 until the measured value of the electricalcapacitance between the pipetting needle 42 and the reference body 45reaches a predetermined value C74 corresponding to a specific distanceS74 between the pipetting needle 42 and the surface of the referencebody 45, and this process is then performed in the opposite direction,that is the pipetting needle 42 is moved in the Y direction towards onesurface 75 of the reference body 45 until the measured value of theelectrical capacitance between the pipetting needle 42 and the referencebody 45 reaches a predetermined value C75 corresponding to a specificdistance S75 between the pipetting needle 42 and the surface of thereference body 45. Within the context of the invention, preferably,C74=C75=C73=C72 and S74=S75=S73=S72.

In this second preferred embodiment of the method for the fineadjustment of the transport device 51-55, the coordinate values of thetwo thus defined positions of the pipetting needle 42 in each of thehorizontal transport directions are preferably detected and stored. Thecoordinate values of a reference position in each of the horizontaltransport directions is determined by calculating the average of the twodetected coordinate values.

After the coordinates Xo, Yo of the above-mentioned reference axis havebeen determined, the X and Y coordinates of all the pipetting positionsof the pipetting needle with respect to Xo, Yo are calculated in theabove-mentioned control unit by reference to the relevant dimensions ofthe different parts of the analyzer.

Arrangement for testing linearity of the pipetting needle

Irrespective of the apparatus and method used for accurate adjustment ofthe pipetting needle transport device, the above-described analyzercomprises an arrangement which allows the linearity of the pipettingneedle to be tested. The arrangement comprises the following means:

means for guiding the tip of the pipetting needle 42 around theperiphery of the top edge of a reference body 45, the tip of thepipetting needle 42 being guided at a specific distance d from the topedge, which distance is a measure of the acceptable curvature of thepipetting needle,

an electrical circuit for detecting electrical contact between the tipof the pipetting needle and the reference body 45, and

a display connected to this circuit, to display unacceptable curvatureof the pipetting needle in response to an output signal from the circuitdetecting electrical contact between the tip of the pipetting needle 42and the reference body 45.

This arrangement is preferably used in combination with theabove-described means for adjusting the transport device 51-55 of thepipetting needle 42.

Method of testing the linearity of the pipetting needle

After accurate adjustment of the transport device 51-55 of the pipettingneedle 42, which is preferably carried out with the above-describedmethod, the linearity of the pipetting needle 42 is tested by thefollowing method. As shown in FIGS. 12 and 13, the tip of the pipettingneedle 42 is guided around the periphery of the top edge of a referencebody 45 along a path 81, 82, 83, 84, the tip of the pipetting needle 42being guided at a specific distance d from the edge of the referencebody 45, which distance is a measure of the acceptable curvature of thepipetting needle. The distance d is, for example, 0.45 mm. The verticalposition of the pipetting needle with respect to the reference body isas shown in FIG. 13. Any contact between the reference body 45 and thepipetting needle 42 is detected by an electrical circuit which in such acase results in the display of an unacceptable curvature of thepipetting needle.

Upon reading the present specification, various alternative embodimentswill become obvious to those skilled in the art. For example, sizes andshapes of various components may be employed to achieve the statedobjectives. These variations are to be considered within the scope andspirit of the invention, which is only to be limited by the claims whichfollow and their equivalents.

What is claimed is:
 1. An analyzer comprising:a) a horizontally disposed baseplate on which primary containers and secondary containers are disposed; b) a metering device for measuring a predetermined volume of a liquid; c) a pipetting needle for transferring a predetermined volume of liquid from a primary container to a secondary container, the pipetting needle being formed of an electrically conductive material and being connected by tubing to the metering device; d) a transport device for the controlled transport of the pipetting needle in three directions at right angles to one another, two of the transport directions extending horizontally and the third transport direction extending vertically; e) an electrically conductive reference body having a top edge and being positioned at a predetermined location with respect to the analyzer; and f) a control device for controlling the metering device and the transport device, the control device comprising:1) means for guiding the tip of the pipetting needle around the the external periphery of the top edge of the reference body, the tip of the pipetting needle being guided at a specific distance from the top edge of the reference body, the distance being a measure of the acceptable curvature of the pipetting needle, and 2) an electrical circuit between the pipetting needle and the reference body for detecting an electrical contact between the tip of the pipetting needle and the reference body.
 2. The analyzer according to claim 1, wherein the electrically conductive reference body is rigidly connected to the baseplate, and in each of the horizontal transport directions has two outer surfaces disposed perpendicularly to the transport direction.
 3. The analyzer of claim 2 further comprising means for determining the coordinates of a reference position of the pipetting needle in at least one of the horizontal transport directions, the means being adapted to move the transport device of the pipetting needle causing the pipetting needle to be moved in opposite directions in each case to a position near each of the two outer surfaces of the reference body which are disposed perpendicularly to the transport direction, the pipetting needle being moved in each case towards a surface of the reference body until the value of the electrical capacitance between the pipetting needle and the reference body, as measured by a circuit, reaches a predetermined value corresponding to a specific distance between the pipetting needle and the surface of the reference body.
 4. The analyzer according to claim 1, wherein the reference body is in the form of a parallelopiped.
 5. The analyzer according to claim 1, wherein the top edge of the reference body is shaped as a square. 